ABSTRACT/PROJECT SUMMARY Nausea and vomiting are frequent and debilitating symptoms experienced by women being treated for breast cancer. These symptoms occur repeatedly due to the surgical procedure, anesthesia during surgery, opioids for pain, adjuvant therapy, especially chemotherapy, and perhaps the disease itself. Current guidelines of the American Society of Clinical Oncology indicate that the goal for treatment-induced nausea and vomiting should be complete control. However, this goal has remained elusive. Results from research show that 20-30% of women continue to experience these symptoms following surgery or chemotherapy, even when well established, evidence based clinical guidelines are followed. Given that over 240,000 women will be diagnosed with breast cancer in 2016, this is a highly significant problem. Treatment-induced nausea and vomiting (TINV) have a profound impact on the health and well-being of women with breast cancer. They are related to significant morbidity (dehydration, wound dehiscence, pain, and immobility), increased length of stay, increased hospital costs and poor patient satisfaction.) Because the factors that influence variability in TINV and the mechanisms underlying TINV are not clearly understood, this innovative study will employ a prospective, comparative design to study 300 women diagnosed with early stage breast cancer (Stage I, II, IIIa) who will be recruited prior to scheduled breast cancer surgery. We hypothesize that substantial variability in TINV occurs during the first year of treatment following surgery for breast cancer, that this variability will cluster into distinct groups and groupings will be explained by individual (age, race, history of nausea and vomiting), disease/treatment (medications) and genomic factors; and co-occurring symptoms (sleep disturbance, fatigue, anxiety, pain). TINV data, using the nausea and vomiting subscale of the Patient-Reported Outcomes Measurement Information System Gastrointestinal (PROMISGI), will be collected prior to initial surgery through one year of treatment. Co- occurring symptoms will be measured using the PROMIS29. TINV is controlled by activation of multiple cellular receptors including those for serotonin, dopamine, histamine, acetylcholine, opioid and substance P. These common neural mechanisms mediate TINV regardless of the etiology and will be the targets for the genomic analysis of this study. An understanding of the precise relationship between these targets and the TINV phenotype, and the stratification of symptoms into subgroups according to their underlying biological mechanisms are required for the development of precision medicine strategies. In addition, a retrospective study using banked samples linked to rich symptom phenotype data (including nausea and vomiting) in women with breast cancer will be completed to address replication of significant genetic findings. The results of this rigorously conducted prospective study will inform subsequent research to develop and test personalized targeted interventions to control TINV in women undergoing breast cancer treatment.